This study is to investigate the anti-tumor activities of a novel cyclophosphamide derivate 4, 6-diphenyl cyclophosphamide (9b) in vivo and in vitro, and its possible mechanism of action. The inhibitory effects of 9b on human hepatoma cell line HepG2, human breast carcinoma cell line MCF-7 and human myeloid leukemia cell line K562 were measured by MTT assay in vitro. Cell cycle distribution and apoptotic rate were evaluated by flow cytometry. To evaluate the anti-tumor effect of 9b in vivo, mouse model bearing inoculated H22 tumor was established. The results indicated that 9b could inhibit the proliferation of HepG2, MCF-7 and K562 cells in a dose and time dependent manner. The ICo50 values of 9b were 32.34 micromol.L-1 to HepG2 cells, 87.07 micromol.L-1 to MCF-7 cells and 149.10 micromol.L-1 to K562 cells after incubation for 48 h. The results of flow cytometry indicated that after being treated for 48 h with different concentrations of 9b, the ratios of HepG2, MCF-7 cells at the Go/G1 phase and K562 cells at the G0/Gl phase and G2/M phase increased significantly compared with control group, and the apoptotic rate increased with the increase of the concentration of 9b. 9b could significantly reduce tumor weight of H22 solid tumor mouse model in vivo. To summarize, 9b showed significantly anti-tumor activity in vivo and in vitro, of which the mechanism might be associated with the change of cell cycle distribution and induction of tumor cell apoptosis.
Animals ; Antineoplastic Agents, Alkylating ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclophosphamide ; analogs & derivatives ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms, Experimental ; pathology ; Male ; Mice ; Molecular Structure ; Random Allocation ; Tumor Burden ; drug effects

OBJECTIVEThe purpose of this study was to explore the relationship between originate and breakout and radiofrequency catheter ablation strategy in patients undergoing radiofrequency ablation for premature ventricular contractions originating from the aortic sinus cusp (ASC) using 3-dimensional electro anatomic mapping.

METHODSThis study included 21 consecutive patients (10 male) underwent ablation for frequent PVCs originating from ASC in our hospital between May 2009 and February 2012. Electro anatomic mapping and ablation of right ventricular outflow track (RVOT) and left ventricular outflow track (LVOT) were performed with the 7F 4-mm-tip ablation catheter from right femoral vein and artery. Activation mapping and pacing mapping were performed in all patients.

RESULTSAblation was successful in all 21 patients successful ablation target in left coronary sinus cusp (LCC, n = 17), in right coronary sinus cusp (RCC, n = 2) and in noncoronary sinus cusp (NCC, n = 2). Seven patients showed a RBBB morphology (group A) and 14 patients showed a LBBB morphology (group B). In group A, earliest ventricular activation (EVA) was recorded 22 - 34 (27.4 ± 4.6) ms earlier before QRS at the site of catheter ablation in ASC. In group B, EVA was later in RVOT than that in ASC in 5 patients and EVA at the site of catheter ablation in RVOT and ASC was 22 - 28 (25.2 ± 2.7) ms and 26 - 40 (32.8 ± 5.2) ms, respectively (t = -3.6, P = 0.024) while EVA was earlier in the remaining 9 patients and EVA recorded in RVOT and ASC was 22 - 38 (28.7 ± 5.9) ms and 18 - 28 (22.7 ± 3.6) ms, respectively (t = 3.8, P = 0.005).

CONCLUSIONPatients with premature ventricular contractions originating from the ASC often show preferential conduction to the RVOT, which may explain the LBBB morphology of ECG in these patients.

Adult ; Aged ; Bundle-Branch Block ; etiology ; pathology ; physiopathology ; Catheter Ablation ; methods ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Sinus of Valsalva ; physiopathology ; Ventricular Premature Complexes ; complications ; pathology ; physiopathology ; Young Adult

OBJECTIVETo explore the electrocardiogram and 3-dimensional electroanatomic mapping features and radiofrequency catheter ablation efficacy of patients with premature ventricular contractions (PVCs ) originating from His bundle region.

METHODSBetween February 2009 and February 2011, 10 consecutive patients ( 4 male, aged from 19 to 59 years) who underwent ablation for frequent PVCs originating close to His bundle region in our department were included. Electroanatomic mapping of RVOT and ASC, ablation was performed with the 7F 4-mm-tip ablation catheter.

RESULTSAmong these 10 patients with PVCs originating from His bundle region, 6 originated from the RVOT, 1 from NCC and 3 from RCC. Eight patients showed LBBB morphology,1 patient with PVCs originated from RCC and 1 patient with PVCs originated from NCC showed RBBB morphology. At the successful ablation sites, local ventricular activation v wave was detected 22-52 (32.6 ± 10.2) ms earlier than the QRS wave in the surface electrocardiogram. The distance between target and His bundle was 5.0-8.4(7.0 ± 1.1)mm. Ablation was successful in all 10 patients without complications (PVCs < 500 beats/24 h post ablation).

CONCLUSIONPVCs originating near the His bundle have similar electrocardiographic and electrophysiological characteristics for PVSc originated from the RVOT or ASC. Because of the close anatomical relationship between RVOT and ASC, it is necessary to mapping both RVOT and ASC to accurately identify the site of PVCs origin and to guild successful ablation.

Adult ; Bundle of His ; surgery ; Catheter Ablation ; methods ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Ventricular Premature Complexes ; surgery ; Young Adult

OBJECTIVE: To evaluate the therapeutic effect of the herbal plaster Tangshangxiaobagao on partial thickness burn wound. METHODS: A randomized controlled trial was conducted with two herbal plasters: Tangshang-xiaobagao and Jingwanhong in 57 hospitalized burn patients. Both the effect and safety of two herbal plasters were noted in patients with partial thickness burns. RESTULTS: In superficial second degree burns, the 7 d healing rate of both groups was (61.35+/-36.26)%and (51.21+/-37.24)% and the healing time (10.56+/-3.43)d and (11.98+/-4.13)d P<0.05 respectively. While in deep second degree burns, the 14 d healing rate of both groups was (62.9+/-36.0) % and (53.9+/-32.2) % and the healing time (19.4+/-4.9)d and (21.5+/-5.5)d, respectively. Study group had lower VAS(visual analogue scale)score than control group. No obvious side effects were observed in study group. CONCLUSION: Tangshangxiaobagao is safe and may be an effective adjunct for treatment of partial thickness burn wounds.

OBJECTIVETo evaluate the prognostic value of plasma brain natriuretic peptide (BNP) and C-reactive protein (CRP) in patients with acute coronary syndromes (ACS) underwent percutaneous coronary intervention (PCI).

METHODSPatients with ACS underwent PCI in our hospital from December 2004 to September 2005 were included in this study. Plasma BNP (n = 189) and CRP (n = 141) were measured at a median of (34.2 +/- 16.3) hours from symptom onset, total mortality and the risk for major adverse cardiac events (MACE, including death, recurrent MI, recurrent angina, heart failure, readmission for any reason) at 30 days and at 3 months was analyzed.

RESULTSPatients were divided into 4 groups according to their BNP levels (BNP 100 ng/L to 300 ng/L to 600 ng/L) and the 3-month mortality was 0%, 1.4%, 7.7%, 48.3% and 3-month incidence of MACE was 7.9%, 17.1%, 57.7%, 79.3% respectively. Multivariate logistic regression analyses showed that the plasma BNP level predicted 30-day (r = 0.8515, P < 0.01) and 3-month (r = 0.9201, P < 0.01) mortality and 30-day (r = 0.7066, P < 0.01) and 3-month (r = 0.7090, P < 0.01) incidence of MACE independent of other known prognostic factors such as age, gender, family heredity, hypercholesterolemia diabetes, hypertension, smoking and LVEF. Patients were divided into 3 groups according to their CRP levels (CRP 8.0 mg/L to 32.0 mg/L) and 3-month mortality was 2.7%, 7.7% and 28.6% and 3-month incidence of MACE was 28.4%, 41.0% and 60.7% respectively. CRP predicted 30-day (r = 0.5882, P = 0.0044) and 3-month (r = 0.5235, P = 0.0038) mortality independent of traditional risk factors, and predicted 30-day (r = 0.2705, P = 0.0380) and 3-month (r = 0.2290, P = 0.0429) incidence of MACE after adjustment for patient age. CRP lost its predictive value after BNP was introduced into the model, while BNP was still an independent predictor for mortality and incidence of MACE at 30 days and 3 months in ACS patients underwent PCI.

CONCLUSIONBoth plasma BNP and CRP are good predictors for early mortality and MACE incidence in ACS patients underwent PCI.

Acute Coronary Syndrome ; blood ; diagnosis ; therapy ; Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon, Coronary ; C-Reactive Protein ; metabolism ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Predictive Value of Tests ; Prognosis

OBJECTIVETo investigate the relationship between hepatitis B virus (HBV) genotype and therapeutic efficacy during the early phase of lamivudine treatment.

METHODSTotally 595 patients with chronic hepatitis B were treated with lamivudine 100 mg/day for 12 months. HBV genotypes, contents of HBV DNA, HBeAg/anti-HBe and YMDD mutation after lamivudine treatment for 12 months were determined. The data were analyzed with SPSS software.

RESULTSIn 595 patients, 8 (1.4%) were genotype A; 53 (8.9%) genotype B; 360 (60.5%) genotype C; 112 (18.8%) were coinfection of genotype B and C; 14 (2.4%) of A and C; 15 (2.5%) A and B; 6 (1.0%) of A, B, and C, and remaining 27 (4.5%) were unspecified. Patients were treated with lamivudine 100 mg/day for 12 months. Genotype B with HBV DNA levels turned to be negative (HBV DNA < 0.1 ng/L) was 87.2%, genotype C was 89.51%, coinfection of genotype B and C was 93.04% (P > 0.05). HBeAg seroconversion of genotype B was 11.65%, of genotype C was 20.64%, and of coinfection of genotype B and C was 18.57% (P > 0.05). All 69 strains of YMDD mutation were detected after lamivudine treatment for 12 months, in which genotype B was in 16.98%, genotype C in 15.38%, and coinfection of genotype B and C was in 13.86% (P > 0.05).

CONCLUSIONThere was no difference in HBV genotypes and the rate of development of YMDD mutations, HBeAg seroconversion, descending of HBV DNA level in Chinese patients with chronic hepatitis B.

China ; Genotype ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; immunology ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Lamivudine ; therapeutic use ; Reverse Transcriptase Inhibitors ; therapeutic use ; Treatment Outcome

OBJECTIVETo study the genetic diversity of HIV-1 nef genes from a patient with AIDS dementia complex(ADC) , so as to research the amino acid variability and the pathogenesis of ADC.

METHODSThe nef gene was amplified with PCR from genomic DNA which was extracted from spleen and different brain tissues(basal ganglia, frontal gray matter, meninges, temporal lobe)of a patient who died of ADC. PCR products were cloned into the pMD19-T vector, after transformation and selection by ampicillin and blue/white spotting. Five of positive clones were sequenced and confirmed with BLAST. HIV-1 nef sequences were processed with BioEdit and MEGA4 to do Neighbor-Joining tree, p-Distances, and values of ds/dn.

RESULTSThe samples were all identified as HIV-1 B and genetic variation exists in HIV-1 nef gene isolated from different tissues compared with HXB2. In addition,part of the changes were different between periphery and brain.

CONCLUSIONVariations exist in the HIV-1 nef gene extracted from the ADC patient and the variations from peripheral and central nerve tissues were different,these variations may change the function of Nef,and it needs more research.

AIDS Dementia Complex ; virology ; Adult ; DNA, Viral ; genetics ; Genetic Variation ; HIV Infections ; virology ; HIV-1 ; genetics ; Humans ; Male ; nef Gene Products, Human Immunodeficiency Virus ; genetics

BACKGROUNDIt is the first multicenter clinical study in China to investigate zanamivir use among Chinese adolescents and adults with influenza-like illness (ILI) since 2009, when inhaled zanamivir (RELENZA(®)) was marketed in China.

METHODSAn uncontrolled open-label, multicentre study to evaluate the antiviral activity, and safety of inhaled zanamivir (as Rotadisk via Diskhaler device); 10 mg administered twice daily for 5 days in subjects ≥ 12 years old with ILI. Patients were enrolled within 48 hours of onset and followed for eight days. Patients were defined as being influenza-positive if the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) test had positive results.

RESULTSA total of 400 patients ≥ 12 years old were screened from 11 centers in seven provinces from March 2010 to January 2011. Three hundred and ninety-two patients who took at least one dose of zanamivir were entered into the safety analysis. The mean age was 33.8 years and 50% were male. Cardiovascular diseases and diabetes were the most common comorbidities. All the reported adverse events, such as rash, nasal ache, muscle ache, nausea, diarrhea, headache, occurred in less than 1% of subjects. Mild sinus bradycadia or arrhythmia occurred in four subjects (1%). Most of the adverse events were mild and did not require any change of treatment. No severe adverse events (SAE) or fatal cases were reported. Bronchospasm was found in a 38 years old woman whose symptoms disappeared after stopping zanamivir and without additional treatment. All the 61 influenza virus isolates (43 before enrollment, 18 during treatment) proved to be sensitive to zanamivir.

CONCLUSIONSZanamivir is well tolerated by Chinese adolescents and adults with ILIs. There is no evidence for the emergence of drug-resistant isolates during treatment with zanamivir.

Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Influenza, Human ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Zanamivir ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUNDMyocardial tissue-level perfusion failure is associated with adverse outcomes following ST-elevation myocardial infarction (STEMI) despite successful epicardial recanalization. We have developed a new quantitative index-thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC)--for assessing myocardial tissue level perfusion. However, factors affecting this novel index of myocardial perfusion are currently unknown.

METHODSA total of 255 consecutive STEMI patients undergoing primary angioplasty were enrolled. Myocardial tissue level perfusion was assessed by TMPFC, which measures the filling and clearance of contrast in the myocardium using cine-angiographic frame counting. We differentiate three groups with two cut off values for TMPFC: a TMPFC of 90 frames was the upper boundary of the 95% confidence interval (CI) for the TMPFC observed in normal arteries, and a TMPFC of 130 was the 75th percentile of TMPFC.

RESULTSSTEMI patients with TMPFC > 130 frames (68 patients, 26.7%) had higher clinical and angiographic risk factor profiles as well as a higher 30-day MACE rate compared with those with TMPFC ≤ 90 frames and those with TMPFC > 90 and ≤ 130 frames. Multivariable analysis identified that the independent predictors of TMPFC > 130 frames were age ≥ 75 years (OR 2.08, 95%CI 1.21 to 3.58, P = 0.007), diabetes (OR 1.37, 95%CI 1.01 to 1.86, P = 0.042), Killip class ≥ 2 (OR 1.52, 95%CI 1.05 to 2.21, P = 0.027), and prolonged pain-to-balloon time (OR 1.73, 95%CI 1.07 to 2.79, P = 0.013). TMPFC > 130 frames was identified as the strongest independent predictor of 30-day major adverse cardiac event (MACE) (OR 2.77, 95%CI 1.21 to 6.31, P = 0.008), along with age ≥ 75 years (OR 2.19, 95%CI 1.11 to 4.33, P = 0.016), female gender (OR 1.67, 95%CI 1.03 to 2.70, P = 0.038), and Killip class ≥ 2 (OR 1.83, 95%CI 1.07 to 3.14, P = 0.021).

CONCLUSIONSSTEMI patients with poor myocardial perfusion assessed by TMPFC had higher risk factor profiles. Advanced age, diabetes, higher Killip class, and longer ischemia time were independent predictors of impaired TMPFC after primary percutaneous coronary intervention. These results emphasize that particular attention should be paid on myocardial microvascular reperfusion in STEMI patients with these risk factors.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; pathology ; therapy ; Myocardial Reperfusion ; Myocardium ; metabolism ; pathology

BACKGROUNDTo explore the cut-off period of subclassification and pathological features of severe hepatitis (SH).

METHODSBased on combined clinical and pathological analyses, the complete clinical and biopsy or autopsy liver tissues data from 196 cases of patients with severe hepatitis were investigated. Meanwhile, proliferative hepatocytes, cholangioepithelia and collagens were identified by a panel of monoclonal antibodies such as those against albumin, cytokeratin 18,19 and collagen I, III with immunohistochemical method.

RESULTSThe clinical and pathological analyses indicated the cut-off periods of acute, subacute and chronic SH (ASH,SSH and CSH) were (13.4+/-7.2) d, (77.4+/-69.3) d and (80.5+/-63.2) d, respectively. Among all SH cases, one case of ASH patient presented clinical manifestation and pathological changes of ASH for 21 days, however, one patient with SSH was demonstrated 12 day course by histological examination. The time of cut-off period between ASH and SSH in child cases was shorter than that in adult cases. Histologically, ASH liver tissues showed massive and/or submassive necrosis caused by one attack, with congestive sinusoid frameworks and proliferative cholangioepithelium-like hepatocytes, while SSH liver tissues presented combined fresh and old submassive or massive necrosis caused by multiple attacks, accompanied by obviously proliferative bile ducts and sinusoid framework collapse.However, the pathological changes of CSH showed ASH- or SSH-like lesions on the background of chronic liver injury.

CONCLUSIONOur data indicated that the cut-off period between ASH and SSH is in accordance with the Scheme of Viral Hepatitis Prevention and Therapy, China, published in 2000, but excluded a part of child SH cases. In our study, the authors found a few pathological features in ASH and SSH.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Collagen ; metabolism ; Female ; Hepatitis ; classification ; metabolism ; pathology ; Humans ; Keratins, Type I ; metabolism ; Liver ; pathology ; Male ; Middle Aged ; Young Adult